To explore the mechanisms of grain dust-induced acute bronchoconstriction, extracts of grain dust were incubated with chopped human lung fragments. The supernatants of the incubation media were examined for the presence of leukotrienes and histamine with high-performance liquid chromatographic techniques. Human lung fragments responded to the extract of grain dust by releasing histamine in a dose-dependent manner. Moreover, leukotrienes (B4, D4, and E4 were also found to be released. The action of grain dust appeared to be independent of the complement pathway or cell cytotoxicity since the lung tissue released the chemical mediators in the absence of plasma and responded to further reaction with compound 48/80 after interaction with grain dust. These data demonstrate that grain-dust extract may induce the release of mediators of anaphylaxis by a nonimmunologic process. This may explain the occurrence of acute bronchoconstriction in some of the grain workers.